In Vitro Activity of a Novel Siderophore-Cephalosporin, GT-1 and Serine-Type β-Lactamase Inhibitor, GT-055, against Escherichia coli, Klebsiella pneumoniaeand Acinetobacter spp. Panel Strains
| Autor: | Roshan D'Souza, Jung-Hyun Byun, Le Phuong Nguyen, Thao Nguyen Vu, Dongeun Yong, Young Lag Cho, Naina Adren Pinto, Hyun-Sook Lee |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Microbiology (medical) Siderophore medicine.drug_class Klebsiella pneumoniae 030106 microbiology Cephalosporin Biology medicine.disease_cause Biochemistry Microbiology GT-055 Article 03 medical and health sciences medicine β-lactamase inhibitor Pharmacology (medical) General Pharmacology Toxicology and Pharmaceutics Escherichia coli Pathogen lcsh:RM1-950 GT-1 Acinetobacter biology.organism_classification In vitro Resistome siderophore-cephalosporin 030104 developmental biology Infectious Diseases lcsh:Therapeutics. Pharmacology |
| Zdroj: | Antibiotics, Vol 9, Iss 267, p 267 (2020) Antibiotics Volume 9 Issue 5 |
| ISSN: | 2079-6382 |
| Popis: | This study investigates GT-1 (also known as LCB10-0200), a novel-siderophore cephalosporin, inhibited multidrug-resistant (MDR) Gram-negative pathogen, via a Trojan horse strategy exploiting iron-uptake systems. We investigated GT-1 activity and the role of siderophore uptake systems, and the combination of GT-1 and a non-&beta lactam &beta lactamase inhibitor (BLI) of diazabicyclooctane, GT-055, (also referred to as LCB18-055) against molecularly characterised resistant Escherichia coli, Klebsiella pneumoniae and Acinetobacter spp. isolates. GT-1 and GT-1/GT-055 were tested in vitro against comparators among three different characterised panel strain sets. Bacterial resistome and siderophore uptake systems were characterised to elucidate the genetic basis for GT-1 minimum inhibitory concentrations (MICs). GT-1 exhibited in vitro activity (&le 2 &mu g/mL MICs) against many MDR isolates, including extended-spectrum &beta lactamase (ESBL)- and carbapenemase-producing E. coli and K. pneumoniae and oxacillinase (OXA)-producing Acinetobacter spp. GT-1 also inhibited strains with mutated siderophore transporters and porins. Although BLI GT-055 exhibited intrinsic activity (MIC 2&ndash 8 &mu g/mL) against most E. coli and K. pneumoniae isolates, GT-055 enhanced the activity of GT-1 against many GT-1&ndash resistant strains. Compared with CAZ-AVI, GT-1/GT-055 exhibited lower MICs against E. coli and K. pneumoniae isolates. GT-1 demonstrated potent in vitro activity against clinical panel strains of E. coli, K. pneumoniae and Acinetobacter spp. GT-055 enhanced the in vitro activity of GT-1 against many GT-1&ndash resistant strains. |
| Databáze: | OpenAIRE |
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